This Center is a multi-disciplinary study of Alzheimer's Disease (AD). Our broadly based resources in geriatrics permit us to study AD patients from several perspectives. We are able, for example, to test hypotheses about the relationship of biochemical findings in cerebrospinal fluid (CSF) to cognitive, brain imaging, and sleep measures. Below is a listing of the major components of the Center and selected hypotheses to be tested within each project and through the integrative analysis of data from independent projects. 1. Core: The Core is responsible for collecting initial screening, diagnosis, and follow-up data at six-month intervals over the course of each patient's illness on demographic, cognitive, medical, and behavioral measures. The major research goal of this component is defining correlates of deterioration in AD. The relative importance of various biological subtypes of AD and psychosocial correlates of clinical decline will be assessed using data derived from the following components. This research may lead to the identification of areas for amelioration even though actual causes of AD remain unknown. 2.Neurobiology Component (Project #1): This component attempts to identify biochemical markers for AD that may be useful in the differential diagnosis of the disease. The neuropathology subcomponent attempts to identify histological markers for subtypes of dementia. Particular attention will be focused on the Lewy Body Variant of AD. A major related question is whether central biochemical changes in dopamine metabolism relate to motor dysfunction and Parkinsonian symptoms often seen in AD and especially in the Lewy Body Variant. 3. Neuroimaging Component (Project #2): The brain imaging component uses CT and MRI measures to follow the natural course of AD with the intention of developing better methods of establishing diagnosis and patterns of deterioration which may provide an empirical basis for AD subtypes. 4. Sleep Component (Project #3): The sleep component examines Sundowning and sleep disturbance as an excess disability in Alzheimer's Disease. Sundowning is defined as nocturnal exacerbation of disruptive behaviors. This project tests several hypotheses linking sundowning to aberrations in the 24-hour body temperature cycle. Preliminary work provides descriptive data on sundowning and explores its sleep/wake, caregiver, and biochemical correlates. This project will yield important information as to why sundowning occurs in AD and may offer clues for chronobiologically-based treatments. 5. Caregiver Assessment and Treatment Component (Project #4): The primary goal of the caregiver component is to study the course of the medical, immunological, psychosocial, and psychiatric status of female spousal caregivers of AD patients. A second goal is to determine if improvement in depression is associated with improved immune system function in clinically depressed caregivers. The present application is a competitive renewal for the Center which has received modest funding since October 1984.